NEUROMUSCLUAR IMMUNOPATHOLOGY IN EAMG-RESISTANT RATS

Gravis(EAMG)，来自两个国家的辅助T细胞之间的免疫学差异 一方面解释疾病易感性的近交系大鼠品系 (在Lewis大鼠中)和抗病能力(在Wistar Furth 老鼠)。这些研究的工作假设是T细胞 Wistar Furth大鼠脑室可能缺乏激活能力 现有B细胞的反应性具有产生 致病抗体；这种特性可能与T细胞缺乏有关 细胞对AChRα表位(S)的反应性 显示Lewis免疫优势的亚基序列Alpha100-116 老鼠。研究将包括对抗体介导的影响的评估。 通过消除这种T细胞而导致的神经肌肉功能障碍 新生大鼠耐受诱导和多肽诱导的反应性 拦截策略。拟议的研究还将评估 在Wistar Furth T细胞特异性谱系中的这一缺陷 将阿尔法100-116反应细胞的频率与 刘易斯反应中观察到的频率；包括在本评估中 将测试WF抗原提呈细胞结合和 呈现可能与脑出血相关的阿尔法100-116肽 Wistar Furth T细胞不能驱动抗AChR抗体应答 具有致病的潜力。

Gravis (EAMG), immunological differences between helper T cells from two inbred rat strains that explain disease susceptibility on the one hand (in Lewis rats) and disease-resistance on the other hand (in Wistar Furth rats). The working hypothesis for these studies is that the T cell compartment in Wistar Furth rats may lack the ability to activate responsiveness by existing B cells that have the potential to produce disease-causing antibodies; this quality may be related to a lack of T cell reactivity toward an epitope(s) contained within the AChR alpha subunit sequence alpha 100-116 that demonstrates immunodominance in Lewis rats. Studies will include an evaluation of effects on antibody-mediated inducible neuromuscular dysfunction by the elimination of this T cell reactivity in Lewis rats by neonatal tolerance induction and peptide blocking strategies. Proposed studies will also evaluate the importance of this deficit in the Wistar Furth T cell specificity repertoire by comparing the frequency of alpha 100-116 responding cells to the frequency observed in the Lewis response; included in this evaluation will be tests for the ability of WF antigen presenting cells to bind and present the alpha 100-116 peptide that may be responsible for the inability of Wistar Furth T cells to drive an anti-AChR antibody response with disease-causing potential.